Grant: Doctoral Research Award: Canada Graduate Scholarships

In retinal neurodegenerative diseases, the progressive loss of the specialized light-detecting cells, termed photoreceptors, and the corresponding impairment of cellular communication can lead to irreversible vision loss. This specialized function of the photoreceptors relies on the formation of distinct cellular compartments: one that contains light-sensitive proteins, while the opposite compartment establishes connections with other neurons. While the presence of these distinct domains is essential to photoreceptor survival and function, it remains unclear how it is established and maintained. We have identified Podocalyxin-like protein (Podxl) as a potential candidate in this process due to its many roles in other tissues and expression pattern in the mouse retina. Herein, we aim to uncover whether Podxl is required for the maintenance of distinct functional compartments in photoreceptors, and if Podxl is involved in vision. To identify the function of Podxl in photoreceptors, we use mouse genetics to delete Podxl only in photoreceptors of the retina. Initial functional experiments show that loss of Podxl in photoreceptors results in significant visual defects, while at the molecular level, our results point to defects in connections with other neurons, precluding proper transmission of the visual information to the brain. In this proposal, I describe a series of cutting-edge experiments that will uncover key players involved in the establishment and maintenance of retinal circuits. This project will make a substantial contribution to the field of neurobiology and will help to better understand neurological diseases associated with the impairment of neuron communication, and more specifically in diseases leading to irreversible vision loss.